1. Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells
- Author
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Alberto Plaja, Juan J. González-Aguilera, Angel Guerra, Miguel A. Peinado, Victor Moreno, Diego Arango, Hiroyuki Yamamoto, Pia Alhopuro, Hafid Alazzouzi, Sérgia Velho, Yasuhisa Shinomura, Manel Armengol, E. Espin, Gianpaolo Suriano, Lauri A. Aaltonen, Raquel Seruca, Gabriel Capellá, and Simó Schwartz
- Subjects
Tumor suppressor gene ,Colorectal cancer ,Mdm2 snp309 ,Polymorphism, Single Nucleotide ,Breast cancer ,Risk Factors ,Genetics ,medicine ,Humans ,Age of Onset ,neoplasms ,Gene ,Polymorphism, Single-Stranded Conformational ,Genetics (clinical) ,Aged ,Aged, 80 and over ,biology ,Homozygote ,Case-control study ,Proto-Oncogene Proteins c-mdm2 ,Genes, p53 ,medicine.disease ,Case-Control Studies ,biology.protein ,Cancer research ,Mdm2 ,Age of onset ,Colorectal Neoplasms ,Letter to JMG - Abstract
Background: Mdm2 is a natural inhibitor of p53 function and its overexpression impairs p53 transcriptional activity. T→G single-nucleotide polymorphism at position 309 (SNP309) of mdm2 induces overexpression of mdm2, but inhibits p53. Objectives: To determine whether SNP309 is a risk-modifier polymorphism in colorectal cancer (CRC) and whether tumour selection of P53 mutations are influenced by SNP309. Methods: Single-stranded conformation polymorphism and automatic sequencing were performed. Results: SNP309 is not associated with the risk of CRC or recurrence of tumours. These data do not over-ride the tumour-selection capabilities of P53 mutations in CRC. However, a significant association with non-dominant-negative P53 mutations (p = 0.02) was found. Conclusions: MDM2 -SNP309 favours tumour selection of non-dominant negative P53 mutations in CRC, which also show an earlier age of tumour onset.
- Published
- 2006
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